Daily light-induced transcription in visual cortex neurons drives downward firing rate homeostasis and stabilizes sensory processing

Balancing plasticity and stability in neural circuits is essential for an animal's ability to learn from its environment while preserving proper processing and perception of sensory information. However, unlike the mechanisms that drive plasticity in neural circuits, the activity-induced molecular mechanisms that convey functional stability remain poorly understood. Focusing on the visual cortex of adult mice and combining transcriptomics, electrophysiology, and in vivo calcium imaging, we find that the daily appearance of light induces, in excitatory neurons, a large gene program along with rapid and transient increases in the ratio of excitation and inhibition (E/I ratio) and neural activity. Furthermore, we find that the light-induced transcription factor NPAS4 drives these daily normalizations of the E/I ratio and neural activity rates and that it stabilizes the neurons' response properties. These findings indicate that daily sensory-induced transcription normalizes the E/I ratio and drives downward firing rate homeostasis to maintain proper sensory processing and perception.